Timothy Fosu-Mensah, Ruben Loftus-Cheek and Jairo Riedewald all made their Premier League debuts for Palace, while there were were Huddersfield debuts for Jonas Lossl, Steve Mounie, Aaron Mooy, Mathias Zanka, Kasey Palmer, Tom Ince and Elias Kachunga.
The away side might have taken the lead inside five minutes when Ince found space inside the Palace box, but the summer arrival could not find a route past Wayne Hennessey in the Palace net.
The newly-promoted outfit were purring, however, and they deservedly made the breakthrough in the 23rd minute when Palace defender Joel Ward turned a low Zanka cross into the bottom corner of the net from close range.
Huddersfield then doubled their lead three minutes later when club-record signing Mounie headed a brilliant Mooy cross into the back of the net to stun the Palace supporters at Selhurst Park.
David Wagner's side might have made it 3-0 in the 33rd minute when Zanka met a deep cross from Mooy, but the 27-year-old's header dropped just wide of the post as Palace, who were all over the place in a defensive area, survived conceding a third goal before the interval.
Wilfried Zaha came closest to registering for Palace in the first period, but the former Manchester United attacker could not find a route past Lossl following a mazy run in the 42nd minute.
It was Palace that had the first chance of the second half after substitute Andros Townsend delivered a dangerous cross towards Christian Benteke, but the Belgian completely missed the ball, and Zaha could not convert at the far post.
Benteke had another clear sight of goal in the 55th minute after sending a powerful header towards the bottom corner, but Lossl made a brilliant save as Huddersfield kept their two-goal lead intact, before keeping out an effort from Zaha just before the hour mark.
Palace improved in the second half, but Huddersfield put the game to bed in the 78th minute when Mounie, who joined the Terriers for £11.5m in this summer's transfer window, scored his second of the match with a well-placed effort after super work from Collin Quaner.
Next up for Palace is a trip to Liverpool next weekend, while Huddersfield will attempt to make it back-to-back wins when they welcome fellow newly-promoted side Newcastle United.